title: S100B transgenic mice develop features of Parkinson's disease.
abstract: OBJECTIVE
  Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Until now, the cause and mechanism of PD are unknown, making further studies necessary. We undertook this study to establish the brain-specific S100B gene transgenic mice and investigate the role of S100B in the development of PD.
  
  
  METHODS
  The hS100B transgenic vector was constructed by inserting the human S100B gene downstream into platelet-derived growth factor (PDGF) promoter, followed by microinjection to produce transgenic mice. Motor coordination ability of mice in the S100B transgenic group (TG), S100B knockout group (KG) and the non-transgenic control group (CG) were measured by the Rota-rod test. The expressions of dopamine D1 receptor (D1DR), dopamine D2 receptor (D2DR), G protein-coupled receptor kinase2 (GRK2), G protein-coupled receptor kinase5 (GRK5), tyrosine hydroxylase (TH) in the brain tissue, and levels of dioxyphenylalanine (DOPA), dopamine (DA), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the midbrain tissue were detected by RT-PCR, Western blotting, and high-performance liquid chromatography-fluorescence detection method (HPLC-FLD), respectively.
  
  
  RESULTS
  Compared with CG, in TG, the motor coordination ability of mice, expressions of D2DR and GRK2, and the level of 5-HT visibly decreased, while the levels of DOPA, DA and its metabolic product HVA increased, the expressions of D1DR, GRK5, TH and 5-HIAA were similar. Compared with CG, no obvious change of detection indexes was observed in KG.
  
  
  CONCLUSIONS
  Overexpression of S100B in the brain resulted in motor coordination impairment, which may have resulted from the downregulation of D2DR and GRK2 expressions, increased DA synthesis and metabolism, and decreased 5-HT level. Therefore, S100B may be a potential cause of pathogenesis in PD.
authors.affiliation: Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Comparative Medical Center, Peking Union Medical College, Panjiayuan No. 5, Chaoyang, Beijing, P.R. China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Liu
authors.forename: Hailin
authors.initials: H
authors.lastname: Wang
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011597:Psychomotor Performance / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D045442:Rotarod Performance Test; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; D012701:Serotonin; D010649:Phenylalanine; D006897:Hydroxyindoleacetic Acid; C496568:GRK2 protein, mouse; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; C517895:Grk5 protein, mouse; D004298:Dopamine; D006719:Homovanillic Acid